Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset.
Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset.
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DOI：
10.1186/1471-2407-14-834
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发表时间：
2014-11-18
期刊：
影响因子：
3.8
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Guo Y;Ma J;Lyu X;Liu H;Wei B;Zhao J;Fu S;Ding L;Zhang J
在非小细胞肺癌（nsclc）中，间变性淋巴瘤激酶（ALK）基因与2号染色体上的棘皮微管相关蛋白样4 （EML4）基因的易位已被确定为致癌驱动突变。有研究表明，EML4-ALK融合与非小细胞肺癌对表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKIs）（如吉非替尼和厄洛替尼）的耐药性有关。相比之下，ALK酪氨酸激酶抑制剂（ALK TKI）克里唑替尼在对抗EML4-ALK的非小细胞肺癌中显示出优越的效果。因此，了解EML4-ALK融合基因的特征以及由此产生的肿瘤的临床特征将对疾病诊断和制定个性化的治疗方案有很大的帮助。研究表明，EML4-ALK易位在不吸烟的非小细胞肺癌患者中更为常见，尤其是女性患者。然而，目前尚不清楚男性患者是否也存在这种情况。在这项研究中，我们确定了一组中国非小细胞肺癌男性非吸烟者的EML4-ALK易位频率。与EML4-ALK易位相关的临床特征也进行了研究。本研究招募了95名中国非小细胞肺癌男性患者。采用一步实时RT-PCR和DNA测序检测EML4-ALK融合基因。我们进一步用RT-PCR检测ALK mRNA的表达水平，用免疫组织化学检测ALK蛋白的表达水平。eml4 - alk阳性癌的临床特征也被确定。我们在95例非小细胞肺癌患者中发现了8例EML4-ALK融合基因，占中国非吸烟男性非小细胞肺癌患者的8.42%。与吸烟习惯无关的中国男性患者（3.44%）相比，有显著性增高。与已发表的数据相比，这一比例也显著高于所有中国吸烟者（8/356或2.25%）或全球吸烟者（2.9%）。有趣的是，EML4-ALK融合基因更常见于年轻患者，并与低分化癌相关。EML4-ALK易位频率与中国男性患者的吸烟习惯密切相关，在男性不吸烟者中易位频率更高。EML4-ALK易位与早发性和低分化癌有关。
The translocations of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene on chromosome 2p have been identified in non-small-cell lung cancers (NSCLCs) as oncogenic driver mutations. It has been suggested that EML4-ALK fusion is associated with the resistance in NSCLCs to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and erlotinib. In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK. Thus, characterization of EML4-ALK fusion genes and clinical features of resulting carcinomas would be a great benefit to disease diagnosis and designing customized treatment plans. Studies have suggested that EML4-ALK translocation occurs more frequently in never-smokers with NSCLC, especially in female patients. However, it is not clear whether this is the case in male patients, too. In this study, we have determined the frequency of EML4-ALK translocation in male never-smokers with NSCLC in a cohort of Chinese patients. The clinical features associated with EML4-ALK translocation were also investigated. A cohort of 95 Chinese male never-smokers with NSCLC was enrolled in this study. EML4-ALK fusion genes were detected using one-step real time RT-PCR and DNA sequencing. We further determined the expression levels of ALK mRNA by RT-PCR and ALK protein by immunohistochemistry in these specimens. The clinical features of EML4-ALK–positive carcinomas were also determined. We have identified EML4-ALK fusion genes in 8 out of 95 carcinoma cases, accounting for 8.42% in Chinese male never-smokers with NSCLC. It is significantly higher than that in all Chinese male patients (3.44%) regardless smoking habit. It is also significantly higher than that in all Chinese smokers (8/356 or 2.25%) or in smokers worldwide (2.9%) by comparing to published data. Interestingly, EML4-ALK fusion genes are more frequently found in younger patients and associated with less-differentiated carcinomas. The frequency of EML4-ALK translocation is strongly associated with smoking habits in Chinese male patients with higher frequency in male never-smokers. EML4-ALK translocation is associated with early-onset and less-differentiated carcinomas.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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